low-dose total lymphoid irradiation in treating patients with refractory chronic graft-versus-host disease after donor stem cell transplant

Conditions: Graft Versus Host Disease

Summary: this phase i trial studies the side effects and best dose of low-dose total lymphoid irradiation (ld-tli) in treating patients with chronic graft-versus-host disease that has not responded to treatment with steroids. ld-tli is a procedure in which all of the body's major lymph nodes are treated with small doses of radiation in order to reset the dysfunctional immune system. ld-tli may work as a treatment for graft-versus-host disease caused by a bone marrow or stem cell transplant.

primary objectives: i. to determine the safety of total lymphoid irradiation (tli) in cohorts of a selected population of refractory chronic graft-versus-host disease (gvhd) patients, given to cohorts with a total cumulative doses of tli of 100, 150, 200, 250 or 300 centigray (cgy). secondary objectives: i. to evaluate the efficacy (failure free survival \[ffs\] at 6 months) of this therapy in the study population. ii. approximate the efficacy at different dose levels using the gvhd summary scores. tertiary objectives: i. determine the effect of this therapy on relevant subpopulations of immune cells in an attempt to elucidate a mechanism of action. outline: this is a dose-escalation study. patients undergo ld-tli daily for 1-2 days. after completion of study treatment, patients are followed up on day 45, at 3 and 6 months, at 1 year, and then every 6 months thereafter.

Eligibility criteria:
inclusion criteria: * patients may have received a prior allogeneic hematopoietic stem cell transplant (allohsct) for any indication and from any donor * patients must have a diagnosis of cgvhd, in accordance with national institutes of health (nih) guidelines; patients with "overlap syndrome" are also eligible; note: patients with recurrent, late onset and/or persistent acute gvhd (alone) are not eligible * patients with chronic gvhd who have been exposed to two or more lines of therapy, including at least one of which was composed of a glucocorticoid and a calcineurin inhibitor are eligible. * patients must have active, but not rapidly progressive, refractory cgvhd; any degree of severity (as per nih criteria) and/or pattern of organ involvement may be considered; that said, patients with more severe and/or extensive chronic gvhd are expected to be the usual candidates for therapy * as above, gvhd should be controlled to a degree that would potentially allow no additional requirement for systemic ist before and following tli =\ = day (d) +45, respectively * the ability to administer protocol doses of tli (i.e., 100, 200 or 300 cgy) without exceeding cumulative doses of radiation must be established; for patients with prior radiotherapy exposure, this determination will be made by dr. greven (or her designee) using published guidelines for excessive organ exposure * karnofsky performance status (kps) \>= 60% * white blood cells \>= 3,000/mcl * absolute neutrophil count \>= 1,500/mcl * hemoglobin \>= 10.0 g/dl * platelets \>= 100,000/mcl * note: if such hematologic abnormalities are present and deemed due to the process of cgvhd, such requirements may be waived with the approval of the pi * patients must have non-hematologic organ function as defined below: * left ventricular ejection fraction (lvef) \> 40% * key pulmonary function tests (pfts) \> 40% * no further criteria for non-hematologic organ function are specified; however, if moderate-to-severe (major) organ function is present, such should be discussed with the pi, as various degrees of non-hematologic organ dysfunction may compromise either (or both) outcomes and toxicity evaluation * if there is concern regarding potential reversibility of any specific organ dysfunction, this issue should be addressed by consultation with an appropriate sub-specialist * ability to understand and the willingness to sign an institutional review board (irb)-approved informed consent document exclusion criteria: * patients with evidence of persistent or active malignancy or uncontrolled infection at the time of study entry * patients who are pregnant or breastfeeding